To analyze the clinical phenotype and genetic basis of a Chinese pedigree affected with Otopalatodigital syndrome type 1 (OPD1). A pedigree which was evaluated at the Department of Endocrinology, General Hospital of the Central Theater Command on December 3, 2020 was selected as the study subject. Clinical phenotype and genetic features of the proband were analyzed. Whole exome sequencing was employed to screen for genetic variants in the proband, and Sanger sequencing was used to verify the candidate variants in the proband's mother, uncle, maternal aunt, and paternal aunt. Pathogenicity analysis was also conducted for the candidate variants. The proband, a 16-year-old male, had shown distinctive facial features including mildly prominent eyebrows, down-slanting palpebral fissures, hypertelorism, and depressed nasal bridge. Additionally, he had clubbing of bilateral thumbs and big toes, and central type diabetes insipidus. Genetic sequencing revealed that he has harbored a heterozygous c.586C>T (p.R196W) missense variant of the FLNA gene (NM_001110556.2), which was also carried by his mother and uncle. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), this variant was classified as likely pathogenic (PM1+PM2_Supporting+PP2+PP3+PS4 Supporting). The heterozygous c.586C>T (p.R196W) variant of the FLNA gene probably underlay the pathogenesis in this OPD1 family. The central type diabetes insipidus in the proband may represent a newly discovered phenotype of OPD1. Above finding has contributed crucial information for the comprehensive understanding of the clinical manifestations and pathogenic mechanisms of OPD1.

Otopalatodigital syndrome spectrum disorders are caused by Filamin A (FLNA) gene mutations. Otopalatodigital syndrome spectrum disorders are a group of rare congenital skeletal dysplasia, with specific craniomaxillofacial features including otopalatodigital syndrome type 1 and type 2, Melnick-Needles syndrome, frontometaphyseal dysplasia, terminal osseous dysplasia with pigmentary defects. The authors describe cases of a young girl with Melnick-Needles syndrome and a young boy with frontometaphyseal dysplasia treated in the Oral and Maxillofacial Surgery Department. Both patients had FLNA gene mutation confirmed with molecular genetic analysis. The authors proposed a 4 step treatment of the malformations with good outcomes both aesthetically and functionally, without complication.